Role of leptin in modulating neuroendocrine function: A metabolic link between the brain-pituitary and adipose tissue

The recently discovered 16 kD protein, leptin, consists of 146 amino acids, is synthesized and secreted by adipose tissue, and impacts feed intake and the neuroendocrine-axis. Leptin was first identified as the gene product found deficient in the obese ob/ob mouse. Leptin, in the rodent, serves as a circulating signal of nutritional status and plays a pivotal role in regulation of body weight, energy expenditure, growth, and reproduction. Information regarding the effect of nutrition on serum leptin concentrations and subsequent luteinizing hormone (LH) and growth hormone (GH) secretion in domestic animals is limited. In the pig, serum leptin concentrations decreased by hr 24 of a 28 hr fast with no change in subcutaneous back fat thickness. However, plasma glucose and serum insulin concentrations were lower in fasted animals compared to fed controls. To examine the effects of metabolic fuel restriction on LH, GH and leptin secretion, ovariectomized (OVX) prepuberal gilts were treated with 2-deoxy-D-glucose (2DG), a competitive inhibitor of glycolysis. Mean serum GH concentrations increased and LH pulse frequency decreased after i.v. administration of 300 mg/kg body weight of 2DG. However, serum leptin concentrations were not changed by 2DG treatment. These results demonstrate that the effects of acute energy deprivation on LH and GH secretion are independent of changes in serum leptin concentrations. Serum leptin concentrations increased with age in the intact prepuberal gilt. Ln addition, estradiol-induced leptin mRNA expression was age and weight dependent in the OVX prepuberal gilt. This increase occurred at the time of expected puberty in intact contemporaries and was associated with greater LH secretion. These data suggest that leptin may serve as a signal for the onset of puberty. Moreover, leptin receptor mRNA was localized in the hypothalamus and anterior pituitary of the pig, suggesting that leptin could act at the brain and(or) pituitary to regulate LH and GH secretion. In addition, leptin stimulated GnRH release from hypothalamic tissue in vitro. Studies with pig anterior pituitary cells in culture demonstrated that leptin treatment enhanced basal LH and GH secretion and suppressed gonadotropin releasing hormone (GnRH) and growth hormone releasing hormone (GHRH) induced increase in LH and GH secretion. Furthermore, intracerebroventricular (ICV) administration of leptin suppressed feed intake and stimulated GH but failed to alter LH secretion in the intact prepuberal gilt. Hypothalamic neuropeptide Y (NPY) is responsive to changes in energy balance and serum leptin concentrations in rodents. ICV administration of NPY suppressed LH secretion and increased GH secretion in the OVX pig. Thus, leptin/NPY may be an important link between metabolic status, the neuroendocrine system, growth, and reproductive processes.